Small volume method for drug release screening using ultrasonic agitation

Acevedo, Andrew J.; Holt, R. Glynn; Desai, D. B.; Zaman, Muhammad H

doi:10.1039/c8an00881g

Cited by 5 publications

(5 citation statements)

References 38 publications

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“…26 Drug Release from Neat Naproxen and Naproxen− Ethyl Cellulose Particles. We conducted small-volume in vitro drug release studies using a protocol developed by Acevedo et al, 20 on the neat naproxen and naproxen−ethyl cellulose microparticles to evaluate the extent to which different particle structures affect drug release. PXRD analysis was first conducted to verify the naproxen polymorph within the microparticles prior to drug release testing.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…All collected particles were collected on filter paper, rinsed thrice with ultrapure water to remove traces of surfactant, and vacuum-dried at room temperature for 8 h prior to structural and polymorphic characterization. Drug-release studies from neat naproxen and naproxen− ethyl cellulose particles made using the protocol described above were conducted using the small-volume method described by Acevedo et al 20 A phosphate-buffered saline (PBS) stock solution was prepared by dissolving a 5 g Gibco PBS tablet into 500 mL of ultrapure water, and the test media used for all samples was 50 mL of the PBS solution. The mass of each particle type used per test was set such that the expected amount of naproxen was ∼2.5 mg. A 60 mL roundbottom, plastic test tube (BRAND, Sigma-Aldrich) was used as the test vessel.…”

Section: ■ Introductionmentioning

confidence: 99%

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Microfluidic Extractive Crystallization for Spherical Drug/Drug-Excipient Microparticle Production

Yeap

Acevedo

2019

Org. Process Res. Dev.

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Granulation is a common manufacturing step for pharmaceutical drug products, which improves powder flowability, compactibility, and ensures tablet content uniformity. Granules of uniform content can conventionally be challenging to obtain due to powder segregation and mixing issues prior to granulation. Spherical crystallizationa method where drug crystals are directly formed into spherical granulesis a promising way to overcome issues with mixing and form granules with uniform content. However, a common challenge of existing quasi emulsion solvent diffusion or solvent extraction methods for spherical crystallization involving miscible solvents in stirred batch vessels is the coarse control over particles sizes, as they are sensitive to multiple scale-up factors (mixing efficiency, impeller and vessel geometry, inlet configuration). This limits the method in terms of content uniformity, which in turn limits the extent to which granules with tunable dissolution profiles can be created. Here, we propose a method for the formation of monodisperse drug-excipient microparticles with tunable release profiles via microfluidic spherical extractive crystallization using drug and excipient-loaded ethyl acetate-in-water emulsions. Monodisperse droplets are generated using microfluidics, and droplet saturation via solvent extraction leads to eventual and direct monodisperse spherical particle formation within minutes. We demonstrate this method using ethyl acetate droplets loaded with naproxen or naproxen and ethyl cellulose, as a hydrophobic drug and drug-excipient model system, respectively, and obtained monodisperse spherical microparticles in both cases. Lastly, preliminary investigations of in vitro drug release from a range of microparticles made from droplets containing different naproxen–ethyl cellulose ratios displayed clear differences in the release profiles. When coupled with microfluidic droplet generators that operate at high volumetric throughputs, this method has the potential to be applied in continuous manufacturing platforms for the production of monodisperse spherical drug particles or drug-excipient composites with excellent content uniformity and tunable release profiles at a kilogram per day scale throughput.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Microfluidic Extractive Crystallization for Spherical Drug/Drug-Excipient Microparticle Production

Yeap

Acevedo

2019

Org. Process Res. Dev.

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“…48 In collaboration with an acoustics expert in the Mechanical Engineering department at Boston University, we showed that drug release kinetics could be tuned by varying input power and distance from the acoustic source to the dissolving tablet. 49 The guiding questions related to the "Assay" processes include:…”

Section: Second Prototype With Automated Sample Preparation (2015-2018)mentioning

confidence: 99%

PharmaChk: a decade of research and development towards the first quantitative, field-based medicine quality screening instrument

Acevedo

Desai

Zaman

et al. 2022

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“…The development of affordable devices (in terms of time/resources consumed and user skills required) for dissolution testing is in its infancy. Research to investigate devices for quantification of drug release to probe differences in dosage form composition are underway [ 32 , 33 ].…”

Section: The Need For More Evidencementioning

confidence: 99%

Evaluation of portable devices for medicine quality screening: Lessons learnt, recommendations for implementation, and future priorities

et al. 2021

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Small volume method for drug release screening using ultrasonic agitation

Abstract: Ultrasound delivered via a microprobe horn allows for tunable and repeatable screening of drug release behavior in small volumes.

Cited by 5 publications

References 38 publications

Microfluidic Extractive Crystallization for Spherical Drug/Drug-Excipient Microparticle Production

Microfluidic Extractive Crystallization for Spherical Drug/Drug-Excipient Microparticle Production

PharmaChk: a decade of research and development towards the first quantitative, field-based medicine quality screening instrument

Evaluation of portable devices for medicine quality screening: Lessons learnt, recommendations for implementation, and future priorities

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